Journal article
Both laminin and Schwann cell dystroglycan are necessary for proper clustering of sodium channels at nodes of Ranvier
The Journal of neuroscience, Vol.25(41), pp.9418-9427
10/12/2005
DOI: 10.1523/JNEUROSCI.2068-05.2005
PMCID: PMC1409814
PMID: 16221851
Abstract
Nodes of Ranvier are specialized axonal domains, at which voltage-gated sodium channels cluster. How axons cluster molecules in discrete domains is mostly unknown. Both axons and glia probably provide constraining mechanisms that contribute to domain formation. Proper sodium channel clustering in peripheral nerves depends on contact from Schwann cell microvilli, where at least one molecule, gliomedin, binds the sodium channel complex and induces its clustering. Furthermore, mice lacking Schwann cell dystroglycan have aberrant microvilli and poorly clustered sodium channels. Dystroglycan could interact at the basal lamina or at the axonglial surface. Because dystroglycan is a laminin receptor, and laminin 2 mutations [merosin-deficient congenital muscular dystrophy (MDC1A)] cause reduced nerve conduction velocity, we asked whether laminins are involved. Here, we show that the composition of both laminins and the dystroglycan complex at nodes differs from that of internodes. Mice defective in laminin 2 have poorly formed microvilli and abnormal sodium clusters. These abnormalities are similar, albeit less severe, than those of mice lacking dystroglycan. However, mice lacking all Schwann cell laminins show severe nodal abnormalities, suggesting that other laminins compensate for the lack of laminin 2. Thus, although laminins are located at a distance from the axoglial junction, they are required for proper clustering of sodium channels. Laminins, through their specific nodal receptors and cytoskeletal linkages, may participate in the formation of mechanisms that constrain clusters at nodes. Finally, abnormal sodium channel clusters are present in a patient with MDC1A, providing a molecular basis for the reduced nerve conduction velocity in this disorder.
Details
- Title: Subtitle
- Both laminin and Schwann cell dystroglycan are necessary for proper clustering of sodium channels at nodes of Ranvier
- Creators
- Simona Occhi - Dibit, San Raffaele Scientific Institute, 20132 Milan, ItalyDesirée ZambroniUbaldo Del CarroStefano AmadioErich E SirkowskiSteven S SchererKevin P CampbellSteven A MooreZulin-L ChenSidney StricklandAntonio Di MuzioAntonino UnciniLawrence WrabetzM Laura Feltri
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.25(41), pp.9418-9427
- Publisher
- United States
- DOI
- 10.1523/JNEUROSCI.2068-05.2005
- PMID
- 16221851
- PMCID
- PMC1409814
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Grant note
- GGP04019 / Telethon NS 043174 / NINDS NIH HHS R01 NS045630-09 / NINDS NIH HHS R01 NS041319 / NINDS NIH HHS GGP030074 / Telethon R01 NS038472 / NINDS NIH HHS R01 NS045630 / NINDS NIH HHS NS 041319 / NINDS NIH HHS NS 045630 / NINDS NIH HHS R01 NS043174 / NINDS NIH HHS
- Language
- English
- Date published
- 10/12/2005
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute
- Record Identifier
- 9984020781102771
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